Kawasaki Disease Lesions Research Articles

Facial nerve palsy may indicate coronary artery lesions in Kawasaki disease.

Facial nerve palsy (FNP) is extremely rare in Kawasaki disease (KD) and the incidence is just 0.9-1.3%. Our objective was to study the clinical features and prognosis of KD accompanied with FNP and to determine whether FNP indicated an increased risk of coronary artery lesions (CALs) in KD. An observational study was performed on 9 patients diagnosed as KD accompanied with FNP in Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China between September 2012 and December 2019. Patients were followed up from September 2012 till September 2020. Clinical features, laboratory and echocardiography findings, treatments, and prognosis were analyzed retrospectively. And the clinical data of patients with FNP (group A, n = 9) were compared to matched KD patients without FNP (group B, n = 27) in order to determine whether FNP indicated an increased risk of CALs in KD. The matching factors included sex, age, days of illness at the intravenous immunoglobulin use, and classic/incomplete KD forms. Clinical data of 9 patients were analyzed in this study. Patients tended to be younger than 24months of age (88.9%) and 55.6% were under 12months. Median onset of FNP was day 10 of illness. Eight patients (88.9%) showed unilateral FNP. The levels of laboratory inflammatory markers (White blood cells count, neutrophil percentage, C-reactive protein, erythrocyte sedimentation rate, etc.) were significantly increased in most cases. CALs were noted in 8 of 9 patients (88.9%). Coronary artery aneurysms occurred in 4 cases (44.4%) and the remaining 4 patients showed coronary artery dilation. All patients were given intravenous immunoglobulin therapy (2g/kg), aspirin (30-50mg/kg/day), and short-term dexamethasone. During follow-up, both FNP and CALs were completely recovered in all patients. The duration time of FNP ranged from 10 to 130days. And the time for CALs to normal ranged from 12 to 282days. The occurrence of CALs was significantly higher in patients with FNP than those without FNP (88.9% vs. 25.9%, P < 0.05). KD accompanied with FNP is rare but may indicate an increased risk of CALs. Clinicians should take KD into consideration when children suffer from long-term fever with FNP, even with incomplete diagnostic features. With a long-term follow-up, both FNP and CALs have a good prognosis. • Facial nerve palsy may indicate an increased risk of coronary artery lesions in Kawasaki disease. • Clinicians should take Kawasaki disease into consideration when children suffer from long-term fever with facial nerve palsy, even with incomplete diagnostic features. • Facial nerve palsy and coronary artery lesions have a good prognosis in a long-term follow-up.

IgA Levels Are Associated with Coronary Artery Lesions in Kawasaki Disease.

Background and ObjectivesKawasaki disease (KD) is an acute systemic vasculitis that affects the coronary arteries. Abnormal immune reactions are thought to contribute to disease pathogenesis. The effect of immunoglobulin (Ig) isotype (IgG, IgA, IgM, and IgE) on inflammatory data and clinical outcomes of patients with KD was examined.MethodsIg levels in 241 patients with KD were measured during the acute, subacute, convalescent, and normal phases of the disease.ResultsCompared with reference Ig values, IgG, IgA, and IgM levels were significantly higher in the subacute phase, while IgE levels were elevated in 73.9% (178/241) of patients with KD in all clinical phases. However, high IgE levels were not associated with clinical outcomes, including intravenous immunoglobulin unresponsiveness and coronary artery lesions (CALs). Significantly more CALs were observed in the high IgA group than in the normal IgA group (44.7% vs. 20.8%, respectively; p<0.01). In addition, IgA levels in the acute phase (p=0.038) were 2.2-fold higher, and those in the subacute phase were 1.7-fold higher (p <0.001), in the CAL group than in the non-CAL group. IgA concentrations increased along with the size of the coronary artery aneurysm (p <0.001). Furthermore, there was a strong correlation between IgA levels and CAL size (r=0.435, p<0.001), with a high odds ratio of 2.58 (p=0.022).ConclusionsHigh IgA levels in patients with KD are prognostic for the risk of CALs.

Vasculitis of Vasa Vasorum and Aneurysm Formation in Kawasaki Disease: Predilection for Coronary Arteries Lesions

<i>Backgrounds</i>. The mechanism causing coronary artery lesions in Kawasaki disease (KD) has not yet been fully clarified. <i>Objective</i>. We hypothesized that the main coronary artery (MCA) segment perfused by the vasa vasorum (VV) arose from the atrial and ventricular branches of peripheral coronary arteries in the myocardium (Type 1 VV externa) is more prone to aneurysm formation than that perfused by Type 2 VV originated from the ostium. <i>Methods and Results</i>. We reviewed the coronary angiography and two-dimensional echocardiogram (2DE) data of KD patients in our hospital and measured the distances from the left coronary ostium to the proximal point of the aneurysm in the left MCA (D1) and to the MCA bifurcation (D2). We found that the ratio of the distances (D1/D2) was negatively correlated with the patients’ age of KD onset, indicating that longitudinal extension of the left MCA aneurysms coincided with the development of Type 1 VV externa. We performed a literature review of KD cases with extracardiac aneurysms and found that 15 patients also had giant aneurysms in the MCA. Also, 8 of 9 extracardiac aneurysm cases whose clear 2DE images were available in the reports, the giant MCA aneurysms seemed to have developed at positions immediately adjacent to the ostium. We assume that the giant coronary aneurysms might be a consequence of the coincidence of aneurysms in the MCA segments perfused by Type 1 and 2 VV externas and reflect a severe inflammation where Type 2 VV externa which is less susceptible to blood flow reduction than Type 1 VV externa is affected. <i>Conclusions</i>. Vasculitis in VV externa with the unique structure originating from and distributing most richly across coronary arteries might induce a vicious circle of hypoperfusion of VV externa and reduced coronary blood flow.

Structure equation model and neural network analyses to predict coronary artery lesions in Kawasaki disease: a single-centre retrospective study

A new method to predict coronary artery lesions (CALs) in Kawasaki disease (KD) was developed using a mean structure equation model (SEM) and neural networks (Nnet). There were 314 admitted children with KD who met at least four of the six diagnostic criteria for KD. We defined CALs as the presence of a maximum z score of ≥ 3.0. The SEM using age, sex, intravenous immunoglobulin resistance, number of steroid pulse therapy sessions, C-reactive protein level, and urinary β2-microglobulin (u-β2MG/Cr) values revealed a perfect fit based on the root mean square error of approximation with an R2 value of 1.000 and the excellent discrimination of CALs with a sample score (SS) of 2.0 for a latent variable. The Nnet analysis enabled us to predict CALs with a sensitivity, specificity and c-index of 73%, 99% and 0.86, respectively. This good and simple statistical model that uses common parameters in clinical medicine is useful in deciding the appropriate therapy to prevent CALs in Japanese KD patients.

Utility of color Doppler echocardiography combined with clinical markers in diagnosis and prediction of prognosis of coronary artery lesions in Kawasaki disease.

The utility of color Doppler echocardiography in the diagnosis and follow-up of Kawasaki disease (KD) with coronary artery lesions (CAL) was analyzed, and the clinical parameters associated with the disease were examined. The general data, the color Doppler echocardiography data and the biochemical indexes from 102 children with KD were analyzed. The patients were divided into a CAL group and a non-coronary artery lesion (NCAL) group based on the presence or absence of CAL. The risk factors for CAL in KD were screened by univariate and multivariate analyses. Among the 102 cases, CAL complications were identified in 47 cases (46.08%). Compared with the NCAL group, the CAL group showed significantly higher incidences of fever duration, increased levels of N-terminal pro B-type natriuretic peptide (NT-proBNP), cardiac troponin I (cTnI), C-reactive protein (CRP), intravenous immunoglobulin resistance, erythrocyte sedimentation rate (ESR), platelets, alanine aminotransferase and aspartate aminotransferase, and significantly lower serum albumin levels (P<0.05). According to the multivariate analysis, fever duration [odds ratio (OR)=2.014], NT-proBNP (OR=3.004), cTnI level (OR=2.638), ESR (OR=1.461) and CRP elevation (OR=1.094) were predictors of CAL in KD. During convalescence, the left and right coronary artery diameters in the CAL group significantly decreased (P<0.05). Color Doppler echocardiography can observe the condition of coronary artery disease in patients with KD in real time and predicts its outcomes, which may be helpful for early diagnosis and long-term follow-up. Fever duration, cTnI, NT-proBNP and ESR levels were correlated with coronary artery diameter, of which the comprehensive use may be more accurate in determining the occurrence of CAL in KD.

An automatic diagnostic system of coronary artery lesions in Kawasaki disease using intravascular optical coherence tomography imaging.

Intravascular optical coherence tomography (IV-OCT) is a light-based imaging modality with high resolution, which employs near-infrared light to provide tomographic intracoronary images. Morbidity caused by coronary heart disease is a substantial cause of acute coronary syndrome and sudden cardiac death. The most common intracoronay complications caused by coronary artery disease are intimal hyperplasia, calcification, fibrosis, neovascularization and macrophage accumulation, which require efficient prevention strategies. OCT can provide discriminative information of the intracoronary tissues, which can be used to train a robust fully automatic tissue characterization model based on deep learning. In this study, we aimed to design a diagnostic model of coronary artery lesions. Particularly, we trained a random forest using convolutional neural network features to distinguish between normal and diseased arterial wall structure. Then, based on the arterial wall structure, fully convolutional network is designed to extract the tissue layers in normal cases, and pathological tissues regardless of lesion type in pathological cases. Then, the type of the lesions can be characterized with high precision using our previous model. The results demonstrate the robustness of the model with the approximate overall accuracy up to 90%.

Oxidised Low-Density Lipoprotein and Its Receptor-Mediated Endothelial Dysfunction Are Associated with Coronary Artery Lesions in Kawasaki Disease.

The study aimed to investigate the role of oxidised low-density lipoprotein (oxLDL)/lectin-like-oxLDL receptor-1 (LOX-1) in coronary artery lesions (CALs) in Kawasaki disease (KD) and of plasma oxLDL concentration in the early prediction of CALs in KD. This prospective study included 80 KD patients, 20 febrile and 20 healthy children. oxLDL, LOX-1 and other parameters were analysed in the acute phase. Plasma oxLDL concentration and LOX-1 mRNA expression in peripheral blood mononuclear cells (PBMCs) were significantly increased in KD patients compared with febrile and healthy children (P < 0.001 and P = 0.022, respectively), particularly in the group with CALs (P < 0.001 and P = 0.027, respectively). Coronary Z-score was significantly correlated with plasma oxLDL concentration and LOX-1 mRNA expression (r = 0.739 and 0.637, respectively; P < 0.01). The sensitivity and specificity of predicting CALs were 71.4% and 77.2%, respectively, at plasma oxLDL concentration ≥ 12.38mU/L. oxLDL/LOX-1 may be involved in CAL development. The plasma oxLDL concentration in the acute phase is a potentially useful biological indicator for predicting CAL in KD patients.

Circulating endothelial glycocalyx components as a predictive marker of coronary artery lesions in Kawasaki disease

BackgroundKawasaki disease (KD) is acute and self-limited vasculitis caused by unknown origin, and the critical complication in KD patients is coronary artery lesions (CALs). The endothelial glycocalyx is a network of membranes luminally covering the endothelium. This study aimed to evaluate the clinical utility of serum glycocalyx components as biomarkers of predicting the onset CALs in KD. MethodsSeventy subjects with complete type KD, 18 subjects as febrile control (FC), and 15 subjects as afebrile controls (AC) were enrolled. Medical, demographic, echocardiography, and laboratory data from the medical records were retrospectively analyzed. Serum syndecan-1 and hyaluronan levels prior to intravenous immunoglobulin (IVIG) therapy were measured at the acute phase, immediately after IVIG, the subacute phase, and the time of discharge at the convalescent phase. ResultsSerum syndecan-1 and hyaluronan levels were higher in the KD group than in the AC and FC groups at all three phases. Further, these levels were compared between KD patients with and without the development of CALs. Serum syndecan-1 and hyaluronan levels at the acute phase were significantly elevated in KD patients with the CALs than in those without CALs. Serum hyaluronan, not syndecan-1, was determined as the most contributory parameter to predict CALs by a multiple logistic analysis. ConclusionsCirculating syndecan-1 and hyaluronan can be useful biomarkers to predict the development of CALs in KD.

Biomarkers of intravenous immunoglobulin resistance and coronary artery lesions in Kawasaki disease.

Currently,there are no reliable indicators for predicting intravenous immunoglobulin resistance and coronary artery lesions in the early stage of Kawasaki disease. A total of 300 patients with Kawasaki disease were studied retrospectively. Laboratory data were compared between the intravenous immunoglobulinresistant (29 patients) and responsive groups, and between the groups with coronary artery lesions (48 patients) and withoutcoronary artery lesions. The intravenous immunoglobulinresistant group had significantly higher D-dimer, globulin, interleukin-6 and serum ferritin levels in comparison to the intravenous immunoglobulin responder group. D-dimer level had a sensitivity of 87.0% and a specificity of 56.3% for predicting intravenous immunoglobulin resistance at a cutoff point of 1.09mg/L. Globulin had a sensitivity of 62.1% and a specificity of 82.3% for predicting intravenous immunoglobulin resistance at a cutoff point of 34.7g/L. Serum ferritin level had a sensitivity of 42.9% and a specificity of 88.8% for predicting intravenous immunoglobulin resistance at a cutoff point of 269.7ng/mL. The patients with coronary artery lesions had higher D-dimer and tumor necrosis factor-α level. D-dimer level had a sensitivity of 50% and a specificity of 78.6% for predicting coronary artery lesions at a cutoff point of 1.84mg/L. Based on analysis by multivariate logistic regression, serum ferritin and globulin were independent risks for intravenous immunoglobulin resistance, D-dimer was independent risk for coronary artery lesions. Elevated serum ferritin, globulin and D-dimer levels are significantly associated with intravenous immunoglobulin resistance in Kawasaki disease. Moreover, serum D-dimer is significantly increased in Kawasaki disease with coronary artery lesions.

Inability of Asian risk scoring systems to predict intravenous immunoglobulin resistance and coronary lesions in Kawasaki disease in an Italian cohort

Since resistance to intravenous immunoglobulin (IVIG) is associated with coronary lesions (CALs) in Kawasaki disease (KD), it is crucial to identify patients at risk to protect them from coronary involvement. The available risk scores to predict IVIG resistance were developed in Asian populations in whom their effectiveness has been proven, but data on non-Asian children are limited. The aim of this study is to evaluate the ability of the Kobayashi, Egami, and Formosa risk scores to predict IVIG resistance and CALs in Italian patients with KD. A multicenter retrospective analysis involving children with KD diagnosed between 2000 and 2015 was carried out: 257 patients were enrolled (57.9% boys, 89.9% Caucasian); 43 patients were IVIG resistant (16.7%). The scores have low sensitivity and specificity in predicting IVIG resistance: respectively, KS 64% and 62.5%, ES 41.4% and 77.4%, and FS 70.8% and 44.9%. The predictive value of the 3 scores for predicting CALs was also poor.Conclusion: Kobayashi, Egami, and Formosa Scores are ineffective in predicting IVIG resistance and coronary involvement in a predominantly Caucasian cohort. A specific score system for mostly Caucasian children with KD is needed enable the early identification of those at risk for CALs who could benefit from intensified treatment. What is Known: • There are several risk scores developed in the Asian population to early identify patients with KD at risk for immunoglobulin-resistance and thus for coronary lesions. • Data are scarce on their effectiveness in non-Asian children. What is New: • We present a comprehensive analysis of the ability of 3 Asian risk scores in a cohort of mostly Caucasian children to predict immunoglobulin resistance and coronary involvement. • Low sensitivity and specificity of the Asian scores for immunoglobulin-resistance and coronary lesions suggest the need for criteria specific for different ethnicities.

Association Between Dose of Glucocorticoids and Coronary Artery Lesions in Kawasaki Disease.

Several studies revealed the efficacy of glucocorticoids on prevention of coronary artery lesions (CALs) in Kawasaki disease (KD) patients. However, impacts of different doses of glucocorticoids on clinical outcomes of KD remain unknown. Using the Japanese Diagnosis Procedure Combination inpatient database, we evaluated KD patients who were treated with normal-dose (prednisolone 0.5-4.0 mg/kg/day) or high-dose (methylprednisolone 10-40 mg/kg/day) glucocorticoids. We investigated risks of CALs and readmission, total hospitalization cost, and length of hospital stay in the acute phase of KD using propensity score matching, stabilized propensity-score inverse probability of treatment weighting, and instrumental variable methods. We identified a total of 3,220 patients with KD who were treated with normal-dose (n = 2,453) or high-dose (n = 767) glucocorticoids in addition to intravenous immunoglobulin. One-to-one propensity-matched analyses with 744 pairs demonstrated no significant differences between the normal-dose and the high-dose groups in risk of CALs (risk ratio [RR] 0.83, 95% confidence interval [95% CI] 0.49, 1.40) and risk of readmissions (RR 0.85, 95% CI 0.65, 1.11). Stabilized propensity-score inverse probability weighting and instrumental variable analyses showed similar results to the propensity score matching analyses. Risks of CALs and readmissions and total hospitalization costs were similar between the normal-dose and the high-dose glucocorticoids groups for patients with KD, whereas total length of hospital stay was shorter in the high-dose group than that in the normal-dose group.

Histopathological aspects of cardiovascular lesions in Kawasaki disease.

Kawasaki disease (KD) is the commonest vasculitic syndrome. It affects medium-sized arteries, principally the coronary arteries. Histologically, coronary arteritis begins at 6 to 8 days after the onset of KD and the inflammation rapidly involves all layers of the artery. This results in severe damage to the structural components of the artery leading to arterial dilation. The inflammatory infiltrate in KD arteritis is characterized predominantly by infiltration of monocytes and macrophages. Activated neutrophils, monocytes and macrophages are believed to be involved in the initial stage of coronary arteritis. Inflammatory cell infiltration may continue for up to 25 days of disease following which the inflammatory cells gradually decline in number. Inflammatory lesions in the arteries are relatively synchronous as they evolve from an acute to the chronic stage. If a giant aneurysm remains or vessel recanalization occurs after thrombotic occlusion of an aneurysm, the remodeling of vascular structures may continue for a much longer time.

CYP2E1 Gene Polymorphisms Related to the Formation of Coronary Artery Lesions in Kawasaki Disease.

Kawasaki disease (KD) is an acute febrile systemic vasculitis that disturbs coronary arteries. Patients' risks of adverse cardiovascular events and subclinical atherosclerosis have been found to significantly increase with polymorphisms of the human cytochrome P450. This current study aims to research the possible relationship between cytochrome P450, family 2, subfamily E and polypeptide 1 (CYP2E1) polymorphisms with KD. We selected 6 tag single-nucleotide polymorphisms (SNPs) of the CYP2E1 gene for TaqMan allelic discrimination assay in 340 KD patients and performed analysis on the clinical phenotypes and coronary artery lesions (CALs). CAL associations of tag SNPs were adjusted for age and gender in the logistic regression. The KD patients with a CC genotype of rs915906 demonstrated a greater proportion of CAL formation (P = 0.009). Furthermore, the GG genotype frequencies of rs2070676 showed a significantly greater risk for CAL formation in KD patients (P = 0.007). However, the SNPs of the CYP2E1 gene did not influence CAL formation in the participating KD patients either with or without high-dose acetylsalicylic acid. Using the expression quantitative trait locus analyses, we found that the SNPs associated with CAL formation in KD also affected CYP2E1 expression in certain cell types. This study is the first to find that the risk of CAL formation is related to CYP2E1 gene polymorphisms in KD patients.

The prevention of coronary arterial abnormalities in Kawasaki disease: Ameta-analysis of the corticosteroid effectiveness.

The use of corticosteroid in Kawasaki disease (KD) remains controversial among current guidelines. The objective of this study is to summarize the effectiveness and safety of corticosteroid to prevent coronary arterial lesions in Kawasaki disease, both as initial and rescue therapy. The Medline, EMBASE, Google scholar, Cochrane Central Register of Controlled Trials databases, ClinicalTrials.gov, and Japanese Institutional Repositories Online were searched for studies up to 31 March 2017. Studies that compared incidence of coronary artery lesions between regimens with corticosteroid and regimen without it in a well-defined controlled group were included. The incidence of coronary artery lesion was analyzed by meta-analysis. Nineteen studies published between 1999 and 2016 fulfilled eligibility criteria. There were 3591 patients included for analysis. There was a significant reduction in incidence of coronary artery lesions with usage of corticosteroid with a pooled odds ratio of 0.72 (95% CI 0.57-0.92; p=0.01) than that without usage of corticosteroid. In general, a greater effect was seen in the patient received corticosteroid as initial and adjuvant therapy with intravenous immune globulin (pooled odds ratio 0.39, 95% CI 0.21-0.73, p=0.007) than those who received corticosteroid as rescue therapy. The risk reduction was statistically significant in Japanese groups (OR 0.56, 95% CI 0.42-0.75 in fixed effects model) but not significant in non-Japanese groups (OR 1.45, 95% CI 0.91-2.30 in fixed effects model). We demonstrated an overall reduction in incidence of coronary artery lesions with the use of corticosteroid as initial and adjuvant treatment for Kawasaki disease.

Predictors for intravenous immunoglobulin resistance and coronary artery lesions in Kawasaki disease

BackgroundTo assess the predictors for intravenous immunoglobulin (IVIG) resistance and coronary artery lesions (CALs) in Kawasaki disease (KD).MethodsA total of 560 KD patients were reviewed retrospectively, including 410 complete KD (cKD) and 150 incomplete KD (iKD) patients. The laboratory data were compared between the IVIG-resistant and IVIG-responsive groups, as well as between the coronary artery lesions (CALs+) and without coronary artery lesions (CALs-) groups.ResultsIn the cKD patients, C-reactive protein (CRP) levels had a sensitivity of 65.52% and a specificity of 62.7% for predicting IVIG-resistance at a cutoff point of >100 mg/L. When albumin <32 g/L, the sensitivity and specificity for predicting IVIG-resistance were 72 and 83.19%, respectively. N-terminal pro-brain natriuretic peptide (NT-proBNP) levels had a sensitivity of 73.91% and a specificity of 76.43% for predicting IVIG-resistance at a cutoff point of >1300 pg/ml. Interleukin-6 levels had a sensitivity of 76.19% and a specificity of 61.59% at a cutoff value of >45 pg/ml. Erythrocyte sedimentation rate (ESR) levels had a sensitivity of 53.26% and a specificity of 64.14% for predicting CALs at a cutoff point of >75 mm/h.In the iKD patients, the sensitivity and specificity for predicting IVIG-resistance were 80 and 54.1% when hemoglobin <110 g/L. When proportion of neutrophils >70%, the sensitivity and specificity for predicting IVIG-resistance were 68 and 66.94%, respectively. ESR levels had a sensitivity of 70.83% and a specificity of 65.81% for predicting IVIG-resistance at a cutoff point of >80 mm/h. NT-proBNP levels had a sensitivity of 78.57% and a specificity of 56.67% for predicting IVIG-resistance at a cutoff point of >360 pg/ml. Interleukin-6 levels had a sensitivity of 70.59% and a specificity of 66.28% at a cutoff value of >25 pg/ml. Interleukin-10 levels had a sensitivity of 64.71% and a specificity of 74.42% for predicting IVIG-resistance at a cutoff value of >8 pg/ml. ESR levels had a sensitivity of 61.82% and a specificity of 65.12% for predicting CALs at a cutoff point of >75 mm/h.ConclusionsThe white blood cell count, proportion of neutrophils, hemoglobin, CRP, ESR, albumin, NT-proBNP, interleukin-6 and 10 may be effective predictors for IVIG resistance and CALs in KD patients.

Predictive factors of resistance to intravenous immunoglobulin and coronary artery lesions in Kawasaki disease.

PurposeWe conducted a study to determine which factors may be useful as predictive markers in identifying Kawasaki disease (KD) patients with a high risk of resistance to intravenous immunoglobulin (IVIG) and developing coronary artery lesions (CAL).MethodsWe enrolled 287 patients in acute phase of KD at a single center. The demographic, clinical and laboratory data were collected retrospectively.ResultsThere were 34 patients in the IVIG resistant group. The IVIG resistant group had significantly higher serum N-terminal-pro-brain natriuretic protein (NT-proBNP) levels (P<0.01) and polymorphonuclear neutrophil (PMN) percentage (P<0.01) in comparison to the IVIG responders. The results yielded sensitivity (78.8%, 60.6%), specificity (58.2%, 90%) and cutoff value (628.6 pg/mL, 80.3%) of NT-proBNP and PMN respectively, in predicting IVIG resistance. Despite IVIG administration, 13 of the 287 patients developed CAL. The patients in the CAL group had higher NT-proBNP levels (P<0.01) and higher PMN percentage (P<0.01). In these patients, the results yielded sensitivity (73.3%, 56.7%), specificity (67.9%, 88.9%) and cutoff value (853.4 pg/mL, 80.3%) of NT-proBNP and PMN respectively, for predicting CAL. The area under the curve (AUC) for predicting resistance to IVIG was NT-proBNP 0.712, PMN 0.802. The AUC for predicting CAL was NT-proBNP 0.739, and PMN 0.773.ConclusionSerum NT-proBNP levels and PMN percentage were significantly elevated in patients with KD with IVIG resistance and CAL. Thus, they may be useful predicting markers for IVIG resistance and development of CAL in KD patients.

Receptor for advanced glycation end products involved in circulating endothelial cells release from human coronary endothelial cells induced by C-reactive protein.

This study was designed to investigate the effect of receptor for advanced glycation end products (RAGE), S100A12 and C-reactive protein (CRP) on the release of circulating endothelial cells (CECs) from human coronary artery endothelial cells (HCAECs). HCAECs were cultured in increasing concentration of CRP (0, 12.5, 25, 50μg/ml) or S100A12 protein (0, 4, 10, 25μg/ml) for 24 hr. CECs were measured by flow cytometry. Small interfering RNA (siRNA) was designed to decrease RAGE level. Fluorescence microscopy and real-time quantitative polymerase chain reaction were used to assess the efficiency of siRNA silencing RAGE. The release of CECs from HCAECs was further evaluated by flow cytometry. CRP caused a significant increase in the release of CECs from HCAECs. The number of CECs increased by about 2-fold in 25 μg/ml CRP-treated group compared to the control group (12.22% compared to 6.82%, P=0.032). But S100A12 failed to increase the release of CECs from HCAECs. Blockade of RAGE by siRNA significantly decreased the release of CECs induced by CRP (13.22% of CRP group compared to 8.77% of CRP+siRNA group, P=0.017). RAGE is involved in the release of CECs induced by CRP, and the effect can be attenuated by silencing RAGE. RAGE may play an important role in endothelial dysfunction in cardiovascular disease. Inhibition of RAGE may be a therapeutic target for coronary artery lesions in Kawasaki disease.

Abstract O.42: Efficacy And Safety Of Treatment With Immunoglobulin Plus Steroid For Kawasaki Disease: A Prospective Observational Study

Background: Non-responders to primary intravenous immunoglobulin (IVIG) therapy with aspirin are at risk of coronary artery lesions in Kawasaki disease (KD). A randomized controlled trial (the RAISE study) indicated that prednisolone + primary IVIG improves responsiveness to treatment and coronary artery outcomes in non-responders to IVIG predicted on the basis of Kobayashi score. The present study aimed to verify the efficacy and safety of prednisolone + primary IVIG in predicted non-responders to IVIG. Methods: We conducted a multicenter, prospective cohort study at 30 hospitals in Japan from July 2012. All KD patients received primary IVIG therapy (2 g/kg/24 h) and, if febrile at diagnosis, oral aspirin (30 mg/kg/day) and were stratified by Kobayashi score into non-responders (score [[Unable to Display Character: &amp;#61619;]]5) and responders (score ≤4). The required sample size to reach statistical significance was 1,500 for KD patients and 500 for non-responders. Results: We enrolled 868 patients with KD by the end of 2013, including 545 (63%) predicted responders and 323 (37%) predicted non-responders. Within the non-responder group, 256 patients received IVIG + prednisolone and 67 patients IVIG alone. The non-response rate to IVIG was significantly lower (17% vs. 55%, p&lt;0.001) and the incidence of coronary artery lesions (Japanese criteria; 5% vs. 11%, p=0.06) non-significantly lower in the IVIG + prednisolone group than the IVIG alone group. These results are similar to those of the RAISE study (non-response rate of 13% and coronary artery lesion rate in non-responders of 3%). There were 10 severe adverse events (i.e., aseptic meningitis 2, liver dysfunction 2, anaphylaxis 1, hypertension 1, ventricular tachycardia 1, bacteremia 1, drug eruption 1, and gait disorder 1) and no significant between-group difference in event rate. Conclusion: Like the RAISE study, our study suggests that prednisolone added to IVIG therapy with oral aspirin reduces the non-response rate and incidence of coronary artery lesions in predicted non-responders to IVIG with KD.

Abstract 81: A retrospective analysis of 274 cases of Kawasaki disease

Purpose: Haematological, biochemical and clinical parameters were retrospectively analysed in a group of patients with Kawasaki disease, to determine predictive variables on the effect of intravenous immunoglobulin (IVIG) therapy. Methods: We studied 274 cases of Kawasaki disease between October 2006 and September 2013 at a single centre (Kawasaki Municipal Tama Hospital, Japan). These cases were analysed on the basis of: (1) Requirement of additional therapy post IVIG (41 cases vs 200 cases not requiring additional therapy) (2) Presence of coronary artery lesions (CAL: Z score≧2.5) within a month (15 cases with CAL, 220 cases without CAL) Haematological, biochemical and clinical parameters including white blood cell, percentage of neutrophils, platelet, total-bilirubin, AST, ALT, Albumin, Sodium, C-reaction protein, Fibrinogen and D-dimmer as well as time to first post-IVIG treatment were compared in the categories shown above. Statistical analysis was performed with Mann-Whitney U test. Differences were considered to be significant when the two-tailed p-value was &lt; 0.05. Results: The percentage of neutrophils, total-bilirubin, AST, ALT, Albumin, Sodium, C-reaction protein, D-dimmer and time to first treatment show significant difference between the groups stratified on the requirement of post-IVIG therapy. In the stratification based on acute CAL- AST, ALT, Albumin and Sodium show significant difference between the groups. Conclusion: We suggest that ratio of neutrophil, total-bilirubin, AST, ALT, Albumin, Sodium, C-reaction protein, D-dimmer and time to first treatment are predictive factors of resistance to single IVIG therapy. Similarly, levels of AST, ALT, Albumin and Sodium are predictive factors of acute coronary artery lesions in Kawasaki disease.

Reversible Splenial Lesions in Kawasaki Disease in a 7 Year Old Boy- First Reported Case in North America. (P6.248)

Reversible Splenial Lesions in Kawasaki Disease in a 7 Year Old Boy- First Reported Case in North America. (P6.248)